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estradiol (EstroGel)

✓ Approved

Ascend Therapeutics · ESR1 · 小分子

什么是 estradiol？

estradiol 是一种小分子，由Ascend Therapeutics研发。该药已获批，用于治疗相关适应症，给药途径：Topical、Transdermal。

药物档案

商品名EstroGel
公司Ascend Therapeutics
药物类别小分子
分子靶点ESR1
给药途径Topical, Transdermal
状态Approved
来源： ClinicalTrials.gov, Ascend Therapeutics

作用机制

分子靶点

estradiol 作用于 1 个分子靶点：

ESR1estrogen receptor 1 (ER, ESR)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

estradiol 针对 2 个适应症，涉及 2 个治疗领域。

治疗领域疾病/病症分期
Reproductive system and breast disordersAtrophic vulvovaginitis✓ Approved
Surgical and medical proceduresHormone replacement therapy✓ Approved

相关研究文献

PubMedAnnals of translational medicine2026-09-10

A comprehensive longitudinal study quantifying the systemic effects associated with ovariectomy and high-dose corticosteroids in a sheep model of osteoporosis.

Bisazza Katie T KT, Nelson Brad B BB, Anthony Russell V RV, Goodrich Laurie R LR et al.

The sheep is a common preclinical model for osteoporosis in humans and allows for robust longitudinal studies. Appropriate characterization of large animal models is necessary prior to selection for preclinical studies. We sought to comprehensively characterize the process of bone loss in a 12-month sheep model of osteoporosis, and report on the sheep clinical pathologies throughout osteoporosis model development. We induced osteoporotic bone loss in 10 sheep via ovariectomy and corticosteroid administration. Over a 12-month period, we performed serial bone density scanning, bone biopsy for microarchitecture and histomorphometry assessment, clinical assessments, and evaluated systemic levels of steroid hormones, as well as hematological and biochemical values. Statistical analysis was performed to compare the outcomes of osteoporotic sheep to healthy age-matched control sheep over time. We successfully induced osteoporotic-like bone loss in the experimental group by observing decreased bone density in the lumbar spine and tibia by 6 months, including changes to bone microarchitecture (i.e., trabecular thinning, decreasing bone volume) and histomorphometry (i.e., decreased trabecular bone ratio) indicative of bone remodeling disruption. We also reported comprehensive systemic changes in the same animals over time. Compared to control animals, we observed a significant disruption to clinical pathology parameters and steroid hormone production in osteoporotic sheep. Osteoporotic model development induced hematological and serological disruptions at 3 months, including neutrophilia, immune cell suppression, electrolyte and protein imbalances, hyperphosphatemia, and elevated liver enzymes. Additionally, administration of corticosteroids appeared to suppress cortisol production over the course of model development, followed by a surge of endogenous cortisol following cessation of corticosteroid treatment. Estradiol surprisingly did not drop to significantly lower levels than controls for the duration of the experiment, suggesting that there are extragonadal sources of estradiol production or dietary sources of phytoestrogens in the sheep differing from humans. Bone loss was induced in sheep within 3-6 months, and the most significant systemic disruptions appear to correlate with timing of high-dose corticosteroids. These findings offer a detailed characterization of the sheep model of osteoporosis, enabling investigators to distinguish the effects of treatment administration from those arising solely from model development.

PMID 42718873
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PubMedmBio2026-09-10

Sex and age differences in antibody responses to seasonal influenza vaccination are mediated by estrogenic upregulation of NF-κB and TNF signaling in B cells.

Park Han-Sol H-S, Yin Anna A, Zhou Weiqiang W, Wenstedt Eliane F E EFE et al.

Sex differences in the humoral immune responses to the seasonal quadrivalent influenza vaccine (QIV) in young adults (YA; 18-49 years old) or high-dose QIV in old adults (OA; 75+ years old) were analyzed to determine how age-related changes, including in steroids, impact sex differences in B cells. Among YAs, females had greater H3N2, but not H1N1, neutralizing antibody titers, and greater proportions of hemagglutinin (HA)+ CD19+ B cells and HA+ memory B cells than males through 28 days post-vaccination (DPV), that was not observed among OAs. Machine learning algorithms illustrated that baseline (0 DPV) steroids, including 17-hydroxyprogesterone, estrogens, and testosterone, as well as HA+ CD19+ B cells and HA+ antibody-secreting B cells (ASCs), were major predictors of seroconversion at 28 DPV, particularly in YA. Single-cell RNA sequencing demonstrated that CD19+ B cells from YA females had greater transcriptional activity at 7 DPV than YA males, with upregulation of genes with estrogen-response elements (EREs) along NF-κB-mediated TNF signaling pathways in B-cell subsets, which was mitigated in OA. Estradiol treatment of ASCs from YA females, but not males, increased the number and size of HA+ IgG+ cells and expression of ERE genes along the NF-κB-mediated TNF signaling pathway,that was inhibited by an estrogen receptor antagonist. Pharmacological inhibition of either NF-κB or TNF signaling blocked the ability of E2 to upregulate antibody secretion in cells from YA females. This study provides mechanistic insights into estrogen-mediated increases in influenza vaccine-induced antibody responses among reproductive-aged females and suggests a role for estrogen signaling in the reduction of sex differences in vaccine-induced immunity with old age. Sex differences in influenza vaccine-induced immune responses become less pronounced with old age, which we hypothesize could be related to changes in circulating gonadal steroids. Our study shows that after receipt of the seasonal influenza vaccine, young adult females, who have elevated estrogenic activity, have more B cells that recognize influenza hemagglutinin; their B cells have greater activity along estrogen signaling and inflammatory pathways, and mount stronger antibody responses than young adult males, with these sex differences being mitigated in old adults. We identify estrogen as a key driver of sex differences in influenza immunity by showing that ex vivo estradiol increases antibody production by B cells through the estrogen receptor and engagement with NF-κB. These findings help explain the biological basis for sex differences in vaccine immunity and suggest that the hormonal environment, not just chronological age, shapes how well a person responds to vaccination.

PMID 42720319
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PubMedChannels (Austin, Tex.)2026-09-10

Physiological 17β-oestradiol inhibits KV7.4 currents via GPER1-dependent PLC/PKC signalling.

Karabatak Elif E, Lau Skye S, Salvage Samantha C SC, Jepps Thomas A TA et al.

KV7.4 channels are important regulators of membrane potential and excitability in multiple tissues and are emerging as key effectors of steroid hormone signaling. Here, 17β-estradiol (E2) was examined as a modulator of recombinant KV7.4 channels expressed in HEK293 cells. Whole-cell patch-clamp recordings showed that acute application of E2 reduced KV7.4 current density. At nanomolar concentrations, both E2 and the alternate GPER1 agonist aldosterone inhibited KV7.4 currents only when G protein-coupled estrogen receptor 1 (GPER1) was co-expressed, indicating a receptor-dependent mechanism. Pharmacological inhibition showed that phospholipase C (PLC) and protein kinase C (PKC), but not adenylyl cyclase, contribute to GPER1-mediated inhibition of KV7.4. In contrast, equivalent experiments performed with KV7.5 channels showed no significant effect of E2 despite GPER1 co-expression, suggesting subtype-selective regulation within the KV7 family. Surface biotinylation experiments suggest that GPER1 co-expression reduced surface KV7.4 expression, with a further reduction observed following E2 treatment. Finally, both E2 and aldosterone negatively regulate the sensitivity of KV7.2-5 activator ML213-mediated relaxation in arteries from female rats. Together, these findings identify KV7.4 as a downstream effector of rapid GPER1-dependent estrogen signaling and suggest that steroid status may influence KV7-targeted therapeutic responses.

PMID 42717828
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PubMedJournal of functional foods2026-09-10

Sakuranetin modulates estrogen receptor signaling in breast cancer cells.

Belgodere Jorge A JA, Nguyen Britney B, Hardgrove Anna M AM, Wheat Stephen W SW et al.

Identification of natural, bioactive compounds has been of interest to the biomedical field, in particular for the treatment of cancer. Flavonoids are a family of compounds, present across many plant species, known for their polyphenolic structure that results in cellular bioactivity. The flavonoid, sakuranetin, is produced due to external stressors, through the naringenin biosynthetic pathway. Binding affinity and docking simulations confirmed sakuranetin binding to the estrogen receptor alpha (ERα) pocket in a manner similar to, but with weaker affinity than 17β-estradiol (E2). Due to sakuranetin having chemical similarities to estrogen, this study evaluated the potential of sakuranetin to act as an endocrine modulator in estrogen receptor-positive (ERα+) breast cancer cell lines. In the ERα + cell lines, MCF-7 and T-47D, sakuranetin treatment induced dose-dependent estrogenic activity (≥ 10 μM). Sakuranetin significantly increased colony formation and cell proliferation in the MCF-7 cell line. Breast cancer cell lines with constitutively active ER through an inserted mutation in the ERα (Y537S) demonstrated no significant changes in estrogenic activity or cellular proliferation following sakuranetin treatment, except at an elevated dose (50 μM). Finaly, sakuranetin treatment enhanced genes associated with ER signaling and significantly increased ERα-mediated gene (PGR and CXCL12) expression. These results support the role of sakuranetin as a natural estrogenic compound.

PMID 42719784
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PubMedBiology of reproduction2026-09-10

Galectin-1 Signaling Dysregulation Impairs Stromal Senescence and Decidualization in Recurrent Implantation Failure.

Huang Xu X, Lin Zhi Z, Chen Min M, Zheng Zi-Meng ZM et al.

Endometrial decidualization is indispensable for embryo implantation, and moderate cellular senescence has recently been recognized as a functional component of this process. However, how this senescence response is regulated upstream and whether its disruption contributes to recurrent implantation failure (RIF) remain unclear. Here, we identify Galectin-1 (GAL1) as a potential regulator of senescence-associated decidual responses in human endometrial stromal cells. Moderate senescence induction in human endometrial stromal cells and primary decidual stromal cells (DSCs) was accompanied by enhanced decidualization responses, which was further supported by the co-localization of senescence markers with bone morphogenetic protein 2 (Bmp2) in the murine decidual zone during early gestation. GAL1 promoted senescence-associated and decidualization responses, whereas GAL1 inhibition or LGALS1 knockdown attenuated these effects. Estradiol and progesterone treatment increased GAL1 secretion and the expression of GAL1-associated extracellular components, while integrin inhibition reduced GAL1-induced decidual responses. In RIF endometrium, GAL1 expression was elevated, whereas genes associated with GAL1 signaling were downregulated in stromal cells, accompanied by reduced senescence marker expression. Collectively, our findings identify GAL1 signaling dysregulation as a potential mechanism underlying insufficient stromal senescence and impaired decidualization in a subset of RIF endometrium, providing new insights into the molecular heterogeneity of RIF.

PMID 42720313
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PubMedJournal of the National Cancer Institute2026-09-10

Endocrine Biomarker Changes in a Randomised Low-Dose Tamoxifen Trial for Breast Cancer Prevention.

Nash Stephen S, Hammarström Mattias M, Thörngen John-Olof JO, Winqvist Ola O et al.

Tamoxifen reduces breast cancer incidence and recurrence, but uptake for primary prevention remains limited, largely because of concerns regarding adverse effects at the standard 20 mg dose. Understanding systemic endocrine effects of lower tamoxifen doses may help improve future prevention strategies. We analysed data from 1,055 healthy women enrolled in the randomised, double-blind, placebo-controlled KARISMA trial, assigned to placebo or tamoxifen 1, 2.5, 5, 10, or 20 mg daily for 6 months. Plasma concentrations of endocrine biomarkers and tamoxifen metabolites were measured at study end. Associations between randomised tamoxifen dose, circulating metabolite concentrations, and endocrine biomarker plasma concentration (estrogens, androgens, progestogens, cortisol, prolactin, and sex hormone-binding globulin (SHBG)), were evaluated. Tamoxifen dose was associated with measurable endocrine changes after six months, most consistently increased SHBG levels, with additional associations observed for cortisol and hydroxyprogesterone. SHBG demonstrated the clearest dose-response relationship, with increasing levels across tamoxifen dose groups and evidence of attenuated increase at intermediate doses. Large relative differences between placebo and 20 mg tamoxifen were additionally observed for estrone, estrone sulphate and estradiol. Unadjusted analyses of circulating endoxifen showed broadly similar endocrine patterns; however, these associations were substantially attenuated after adjustment for randomised tamoxifen dose. Circulating tamoxifen metabolites were strongly correlated with administered dose and with one another. Low-dose tamoxifen was associated with measurable endocrine changes, particularly in SHBG, cortisol, and hydroxyprogesterone. These findings show endocrine pharmacodynamic responses during low-dose tamoxifen therapy warrants further investigation as a potential component of future individualised prevention and adjuvant endocrine therapy strategies. ClinicalTrials.gov ID: NCT03346200.

PMID 42720596
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